Journals
2025 EN
Gaillard François · Rabah Melissa Ould · Aubert Olivier
+6 more
ABSTRACT Background Estimating glomerular filtration rate (eGFR) in kidney transplant recipients (KTR) typically relies on plasma creatinine, which is influenced by muscle mass. Reduced muscle mass is suspected to reduce eGFR performance in this population but this effect has not been rigorously evaluated. This study quantified the impact of muscle mass on eGFR accuracy and its confounding effect on the association between kidney function and mortality in KTR. Methods We studied a prospective and consecutive cohort of 1829 KTR (mean age 52 ± 14 years; 38.9% female) who underwent GFR measurement using iohexol clearance (ioGFR). Muscle mass was assessed by creatinine excretion rate (CER) from timed urine collections. We evaluated the impact of muscle mass on the performance of five eGFR equations (MDRD, CKDEPI 2009 , CKDEPI 2021 , EKFC and RFKTS) using multiple regression and subgroup analysis. The association between eGFRs, ioGFR and mortality was examined using Cox proportional hazards models. Results All eGFR equations showed a significant negative correlation with CER. EKFC was the least sensitive to CER ( β coefficient 95% confidence interval [CI]: −0.17 to −0.12). All eGFR equations demonstrated reduced accuracy in the lowest muscle mass tertile. In multivariable analyses, ioGFR was significantly associated with mortality (hazard ratio 95% CI: 0.972–0.995) but eGFRs were not. Including CER in the Cox models resulted in convergence of the mortality hazard ratios for ioGFR and eGFRs (hazard ratio 95% CI: ioGFR: 0.98–0.999; MDRD: 0.98–0.999; CKDEPI 2021 : 0.99–1; EKFC (0.98–1) RFKS: 0.98–0999). Conclusion The performance of all tested creatinine‐based eGFR equations is strongly impacted by muscle mass. Muscle mass is also a key confounder in the mortality risk assessment using eGFR. Incorporating muscle mass into KTR's evaluations may improve kidney function assessments in KTR.
Journals
2025 EN
Paśniewski Maciej · Poleunis Claude · Delcorte Arnaud
+4 more
ABSTRACT Focused ion beam‐scanning electron microscopy (FIB‐SEM) is a microscopy technique that can be used to investigate the quality and structural properties of industrial materials such as polyolefins. An understudied aspect and possible drawback of the technique could be the implantation of the impinging ions under the sample surface and damage to the molecular structure, hindering its use as a sample preparation tool for surface‐sensitive techniques. We systematically investigated the damaging effects of gallium liquid metal focused ion beam under grazing incident beam angle and various accelerating voltages on polyethylene. Changes in molecular structure and ion implantation depth were analyzed with Time‐of‐Flight Secondary Ion Mass Spectrometry (ToF‐SIMS) depth profiling and optical profilometry. Our results show that the gallium ion beam causes significant damage to the polyolefin structure, which is especially observed as dehydrogenation of the molecular structure of the (sub)surface. These molecular products are concentrated in distinct sub‐surface zones, where damage is coupled to the presence of implanted gallium from the FIB etching.
Journals
2025 EN
Puttemans Jedidja · Brammerloo Yasmine · Blibek Karim
+20 more
ABSTRACT Extracellular vesicles (EVs) are known to facilitate infection by enveloped RNA viruses including the Human T‐cell leukemia virus type‐1 (HTLV‐1). HTLV‐1‐encoded proteins, like the transactivator and oncoprotein Tax‐1, are loaded into EVs but their precise impact on EV cargos is not yet known. Here, we report a comprehensive interaction map between Tax‐1 and the human PDZ (PSD95/DLG/ZO‐1) proteins that regulate EVs formation and composition. We show that Tax‐1 interacts with more than one‐third of hPDZome components, including proteins involved in cell cycle, cell–cell junctions, cytoskeleton organization and membrane complex assembly. We extensively characterized Tax‐1 interaction with syntenin‐1, an evolutionary conserved PDZ hub that controls EV biogenesis. Using nuclear magnetic resonance (NMR) spectroscopy, we have determined the structural basis of the interaction between the C ‐terminal PDZ binding motif of Tax‐1, and two PDZ domains of syntenin‐1. Importantly, we show that a small molecule able to inhibit HTLV‐1 cell‐to‐cell transmission breaks the Tax‐1/syntenin‐1 interaction, impacts the levels of syntenin‐1 and viral proteins in EVs, and shifts the EV composition toward cellular antiviral proteins and microRNAs, including the miR‐320 family. Consequently, we demonstrate that mimics of miR‐320c, encapsulated into EVs, have antiviral activities with a potential to be used against HTLV‐1 induced diseases.
Journals
2025 EN
Magdalenic Katarina · Morillon Donatien · De Jonghe Steven
+6 more
ABSTRACT Cancer chemotherapy is continuously challenged by serious complications like pronounced side effects and multidrug resistance (MDR). Natural products, such as curcumin, offer promising alternatives due to their diverse biological applications and low toxicity. However, curcumin's clinical utility is limited by poor bioavailability, rapid metabolism, and non‐specific (PAINS) activity. Building on previous findings, this study explored the structural modification of curcumin‐inspired benzothiazepane derivatives in an attempt to enhance their therapeutic potential through modifications of the two peripheral (hetero)aromatic rings and the benzothiazepane scaffold. In this way, eight new 2‐(hetero)aryl‐4‐(4‐(hetero)aryl‐2‐oxobut‐3‐en‐1‐ylidene)benzothiazepanes and two 4‐thiobutan‐2‐one “double Michael addition” derivatives were synthesized and tested for cytotoxicity against a panel of eight cancer cell lines. The screening results indicated that bis‐(4‐hydroxyphenyl) analogs bearing a chlorinated benzothiazepane ring exhibited the highest potency and broad‐spectrum activity at the low micromolar range. Bis‐substitutions with 3‐pyridinyl and 2‐furyl groups showed less potent but more specific activity profiles, potentially reducing PAINS effects. 2‐Aminothiophenol‐derived double Michael addition products demonstrated increased broad‐spectrum activity, highlighting the importance of the free aniline amino group for targeted effects. This study underscores the potential of benzothiazepane derivatives as viable cancer cell cytotoxic agents and provides useful insights for future optimization and evaluation.
Journals
2025 EN
Fernández Villalobos Nathalie Verónica · Helfenstein Fabrice · Khol Vohith
+25 more
Abstract Introduction In 2016, the World Health Organization recommended differentiated service delivery (DSD) as a client‐centred approach to simplify HIV care in frequency and intensity, thus reducing the clinic visit burden on individuals and HIV programmes. We describe the scale of DSD implementation among HIV facilities in low‐ and middle‐income countries (LMICs) in Latin America, Africa and the Asia‐Pacific before the COVID‐19 pandemic. Methods We analysed facility‐level survey data from HIV care facilities participating in the International epidemiology Databases to Evaluate AIDS consortium in 2019. We used descriptive statistics to summarise the availability of DSD, multi‐month dispensing (MMD) and DSD for HIV treatment models. We explored factors associated with DSD implementation using multivariable models. Results We included 175 facilities in the Asia‐Pacific ( n = 30), Latin America ( n = 8), Central Africa ( n = 21), East Africa ( n = 74), Southern Africa ( n = 28) and West Africa ( n = 14). Overall, 133 facilities (76%) reported implementing DSD. Of these, 91% offered DSD for HIV treatment, 61% for HIV testing and 59% for antiretroviral therapy (ART) initiation. The most common duration of ART refills for clinically stable clients was 3MMD, (70%), followed by monthly (14%) and 6MMD (10%). Facility‐based individual models were the most frequently available DSD for the HIV treatment model (82%), followed by client‐managed group models (60%). Out‐of‐facility individual models were available at 48% of facilities. Facility‐based individual models were particularly common among facilities in East (92%) and Southern Africa (96%). Facilities in medium and high HIV prevalence countries, and those with 3MMD, were more likely to implement DSD. Conclusions In 2019, DSD was available in most HIV care facilities globally but was not evenly implemented across regions and HIV services. Most offered facility‐based DSD for HIV treatment models and 3MMD for clinically stable clients. Efforts to expand DSD for HIV testing and ART initiation and to offer longer MMD can improve long‐term retention in care of people living with HIV in LMICs, while further alleviating the operational burden on healthcare services. These findings from the pre‐COVID‐19 era he need for strengthening DSD in HIV care, which remains at the centre of current efforts towards client‐centred care.
Journals
2025 EN
Fang Shona · Furegato Martina · Azzi Jessica
+2 more
Abstract Wilson disease (WD) is a rare inherited copper metabolism disorder characterized by progressive pathological deposition of copper, primarily in the liver and brain. This longitudinal retrospective study conducted using the French national claims (Système National des Données de Santé [SNDS]) database assessed WD prevalence in France, described patients' characterizations and healthcare resource use and associated costs. Patients with WD were identified from SNDS using the International Classification of Diseases, 10th Revision code E83.0 for copper metabolism disorder or a long‐term disease (affection de longue durée [ALD]) associated with this code between 2010 and 2019. Patients were categorized into hepatic, neurological, and psychiatric sub‐cohorts. We identified 2287 patients with WD yielding a crude prevalence of 1 case per 33 898 individuals in 2019. The mean age at inclusion was 39.9 (standard deviation [SD] 22.8) years, 11 years more than that of the incident cohort (28.6, SD 20.3) identified via ALD, and 1180 (51.6%) patients were male. The crude mortality was 3.2% (in total 370 patients died). Overall, 1011 (44.2%), 754 (33.0%), and 414 (18.1%) patients experienced hepatic, neurological, and psychiatric manifestations, respectively. In total, 922 (40.3%) patients were reimbursed for WD‐specific treatment, the most common being D‐penicillamine (74.8%), and 201 (8.8%) underwent liver transplantation. The average annual hospitalization cost per patient was 4273.7€ (SD 11916.0). At least one sick leave was reported for 533 (23.3%) patients, with an annual average cost of 788.7€ (SD 1328.6). Our findings provide an updated understanding of the prevalence of WD, and indicate a considerable level of morbidity in this population, as well as a high level of direct/indirect costs associated with WD.
Journals
2025 EN
Williamson Harriet · Dominique Laura
ABSTRACT The Appropriate Adult role is one safeguard implemented in England and Wales to support vulnerable suspects in custody. Research has demonstrated this role is a complex one, however, there is limited research exploring police officers' perspectives. This study aimed to investigate their experiences and perceptions of this role. A qualitative approach was adopted, conducting semi‐structured interviews with 15 serving or retired police officers. Following an Interpretative Phenomenological Analysis, two superordinate themes, ‘Understanding and Expectations of the Appropriate Adult Role’ and ‘Experiences Working with Appropriate Adults’ emerged alongside six subordinate themes. Results indicated that participants perceive the Appropriate Adult role as supportive yet reported issues regarding access and parents' emotional involvement. Although these findings demonstrate an increased understanding, there is still confusion surrounding the role. This research provides a novel perspective surrounding Appropriate Adults, having implications surrounding the treatment and support vulnerable suspects are receiving in custody.
Journals
2025 EN
Rodrigues Aaron J. · Marmerstein Joseph T. · Kotamraju Bhanu P.
+2 more
ABSTRACT The vagus nerve, serving as a pivotal link between the brain and vital organs, regulates crucial physiological functions. It plays a central role in maintaining homeostasis within the body and must dynamically adapt to changing conditions such as anesthesia or sleep. While vagal tone, typically estimated indirectly from heart rate variability, has been extensively studied, direct measurement of vagal activity during sleep and anesthesia remains unreported to date. Recent technological advancements have facilitated the recording of vagus nerve activity in freely moving rodents using small, highly flexible carbon nanotube yarns. Consequently, it is now feasible to directly investigate vagal activity during events known to impact homeostasis, such as diurnal variations and anesthesia. In this study, we explore the relationship between anesthesia and vagus nerve activity by comparing the effects of 2% isoflurane anesthesia with activity in freely moving male Sprague Dawley rats. The findings reveal that 2% isoflurane anesthesia significantly suppresses vagus nerve activity, and normal activity levels do not resume until 2 h after the termination of the anesthesia supply. Additionally, we examine the influence of diurnal variations on vagus nerve activity and observe a notable presence of diurnal variations in vagal activity patterns. These results provide insights into the interaction among anesthesia, diurnal variations, and vagal tone, offering valuable understanding of the autonomic nervous system during critical physiological states.
Journals
2025 EN
Wallon Laura · Salonen Anniina · Langevin Dominique
Abstract Surfactant monolayers modify the surface tension of fluid surfaces, and they confer to the surfaces a resistance to mechanical perturbances, such as compression or dilatation. The resistance can be characterized by elastic and viscous moduli, that affect the phenomena involving the motion of liquid surfaces such as wetting, two‐phase flow, foaming and emulsification, rheology and stability of foams and emulsions. Some of these phenomena, for instance coalescence of bubbles or drops, are extremely rapid, and although coalescence seems correlated with the elastic compression modulus, no quantitative comparison has been made. Indeed, this modulus is frequency dependent, and cannot be measured by most conventional devices at the short timescales during which coalescence events occur. In this paper, we first review the current understanding on foam and emulsion stability, highlighting the role of surface rheology in the stability of these systems, important for their formulation. We present tension measurements for various surfactant systems, nonionic and cationic, at oil–water interfaces. We show calculations of the high frequency elastic modulus using the Gibbs adsorption equation and compare the results to previous measurements at air–water interfaces. The moduli measured imposing a rapid expansion of the monolayers are consistently smaller, in particular at oil–water interfaces. We discuss the possible origin of the differences between the two types of interfaces.
Journals
2025 EN
Faure Jean Michel · LarroqueDevigne Anne · Forgues Dominique
+5 more
Objectives Abnormal relative positioning of the superior mesenteric artery (SMA) and vein (SMV) can lead to intestinal malrotation that predisposes to midgut volvulus. The aim of this study was to assess the prenatal ultrasound ability to visualize the relative position of SMA and SMV in normal pregnancies. Methods Prospective cohort study performed in Montpellier University Hospital Centre, including 80 fetuses during routine 3rd trimester ultrasound scan. For each fetus included, the relative position of the vessels on an axial image was defined as SMV on the right, forward, or on the left of SMA. Doppler imaging was additionally used if necessary. Data were compared to the neonatal abdominal scans performed by pediatric radiologist. Results The superior mesenteric vessels were identified in 79 fetuses. Prenatal findings showed a usual relative position of the vessels, that is, the vein on the right of the artery, in 96.2%. In 2 cases, the vein was strictly in front of the artery, and in 1 case, the vein was on the left side of the artery. Seventy‐four neonates were examined and comparison with prenatal finding showed a perfect agreement (Kappa coefficient of 100%). An intestinal malrotation was postnatally diagnosed corresponding to the case where vein was on the left side of the artery. Conclusion This study showed that the relative position of the SMA and SMV could be assessed using ultrasound prenatal examination with a perfect agreement with postnatal findings. In case of abnormal vessels positioning more examinations should be promote including prenatal MRI and postnatal conventional radiologic examinations to confirm intestinal malrotation.